Networks and genes modulated by posterior hypothalamic stimulation in patients with aggressive behaviours: Analysis of probabilistic mapping, normative connectomics, and atlas-derived transcriptomics of the largest international multi-centre dataset

Abstract

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as treatment for refractory aggressive behaviour, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. 91% of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral posterior hypothalamic area and normative connectomic analyses identified fiber tracts and interconnected brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and the amygdala, together with patient age, was highly predictive of treatment outcome. Finally, transcriptomic analysis showed that genes involved in mechanisms of aggressive behaviour, neuronal communication, plasticity and neuroinflammation may underlie this functional network.

Reduction of aggressive behaviour following hypothalamic deep brain stimulation: involvement of 5-HT1Aand testosterone

“…More recently, DBS of the posterior region of the hypothalamus has been investigated for the treatment of aggressive behaviour in patients who exhausted all available medical treatments. Overall, trials in which pHyp-DBS was used to treat aggressive behaviour have shown an average improvement of 91%, with no severe permanent side effects [17,58]. Despite these striking results, the mechanisms responsible for the symptomatic effects of this therapy remain largely unknown.…”